»
Biological Evaluation

Our research group has successfully demonstrated that the introduction of benzene, pyridine and thiophene rings into the core Lipoxin structure has contributed to an enhancement of the biological profile of this class of eicos-anoid 1, 2 . There is an on-going effort in the pharmaceutical industry to design and synthesise new drugs to combat existing inflammatory disorders. These novel stable LXA4 analogues possess the ability to aid the inflammation process and are therefore showing potential...

It has recently been demonstrated that replacement of the triene system, present in native LXA4 and LXB4 with benzene, increases the stability of these eicosanoids to enzymatic metabolism 1-3 . In Chap. 4, we demonstrated that the addition of a heteroatom can also enhance the bioactivity. This pyridine-containing analogue displayed an impressive ability to resolve the inflammation process 4 . In an extension to this work, we sought to replace the triene system with a thiophene ring, Fig. 5.1,...

An alternative strategy to drug design and discovery stems from investigating the secondary metabolites produced by humans instead of plants, animals or microorganisms. This rationale is inspired from the beneficial effects that the plant and microbial metabolites have on the host organism. Prostaglandins are a group of lipid mediators derived from the oxidation of C20 essential fatty acids 9 . They are produced on demand within the cell from arachidonic acid. These short lived messenger...

Another important class of secondary metabolites, oxygenated derivatives of arachidonic acid, were discovered and identified from human leukocytes by Serhan and Samuelsson in 1984 13, 14 . Lipoxin A4 (LXA4) and Lipoxin B4 (LXB4), Fig. 1.5, are trihydroxytetraene-containing eicosanoids. They are produced by the sequential actions of lipoxygenases (LO) during a series of complex cellular interactions 13 . LO are a family of iron-containing enzymes, which are known to catalyse the oxygenation of...